Central venous catheters (CVCs) are indispensible devices for medical practice, particularly among critically ill patients, cancer patients, and those that receive intravenous feeding. These devices allow for the rapid infusion of concentrated medications, fluids, or blood products that can otherwise not be administered via a standard intravenous catheter inserted into a peripheral extremity vein. Although such catheters supply necessary vascular access, they also put the patient at risk for significant infection, which can be life-threatening.
There are an estimated 3 million CVCs inserted each year in the USA and 200,000 in Great Britain (Little and Palmer, Nursing Standard 12:42-44, 1998). In the USA, such catheters remain in place for an estimated 15 million catheter days (1 catheter in 1 patient for 1 day=1 catheter day) in ICUs alone (Mermel, Ann. Intern. Med. 132:391-402 (2000). Catheter-related bloodstream infection is the most frequent cause of hospital-acquired bacteremia (Valles et al. Clin. Infect. Dis. 24:387-395 (1997). 80,000-400,000 central venous catheter (CVC)-related bloodstream infections (CRBI) occur in the USA annually, hospital stay is prolonged by an average of a week, and 2,400-60,000 patients die (Mermel, Ann. Intern. Med. 132:391-402 (2000); Raad and Darouiche, Curr. Opin. Crit. Care 2:361-3651996; Arnow et al., Clin. Infect. Dis. 16:778-784 (1993); CDC, National Nosocomial Infections Surveillance System (NNIS) report, data summary from October 1986-April 1998, issued June, 1998. Am. Infect. Control 26:522-533, (1998); Digiovine et al., Am. J. Respir. Crit. Care Med. 160:976-981 (1999); Rello et al., Am. J. Respir. Crit. Care Med. 162:1027-1030 (2000); Soufir et al., Infect. Control Hosp. Epidemiol. 20:396-401 (1999); Kluger and Maki, Abstracts of the 39th Interscience Conference on Antimicrobial Agents and Chemotherapy. San Francisco, Calif.: American Society for Microbiology, 514 (1999)). Estimates of the annual cost of caring for the CVC-related infections in these patients ranged from $296 million to $2.3 billion in 2000 (Mermel, Ann. Intern. Med. 133:395 (2000)). The use of needleless catheter devices has been associated with an increased risk for bloodstream infection (Kellerman et al., J. Pediatr. 129:711-717 (1996); Do et al., J. Infect. Dis. 179:442-448, (1999)).
Most catheter-related bloodstream infections (CRBI) associated with the use of long-term catheters (>10 days) stem from endoluminal contamination and subsequent colonization of the catheter hub. The hub may become contaminated when microorgansims are present on the external hub surface from contact with the patient's skin, tracheostomy secretions, wounds, ostomy and feces, and the like, or from transfer to the hub surface from the physician or nurse manipulating the catheter (Cicco et al., Lancet 2:1258-1260 (1989)). Most episodes of CRBI are caused by coagulase negative staphylococci, Staphylococcus aureus, enterococci species, Klebsiella pneumonia, Escherichia coli, and Candida species (CDC. Guidelines for the prevention of intravascular catheter-related infections. MMWR 51:1-29, (2002)).
The catheter hub (junction of the catheter and intravenous tubing) has been identified as the primary source of CRBI in patients that have an indwelling catheter for >10 days (Sitges-Serra and Linares, Lancet 1:668 (1983); Sitges-Serra et al., Surgery 97:355-257 (1985); Sitges-Serra et al., JPEN 8:668-672 (1984); Linares et al., J. Clin. Microbiol. 21:357-360 (1985); Forse et al., Surgery 86:507-514 (1979); Moro et al., Infect. Control Hops. Epidemiol. 15:253-264 (1994); Llop et al., Clin. Nutr. 20:527-534 (2001); Bouza et al., J. Hosp. Infect. 54:279-287, (2003); Salzman and Rubin, Nutrition 13:15S-17S (1997); Tan et al., J. Infect. Dis. 169:1393-1397 (1994)). The hub is often contaminated during manipulation necessary to draw blood samples, administer medication, fluid, or parenteral nutrition. Microorganisms present on or nearby (ostomy, wound, fistula, skin, tracheostomy, blanket/clothing) the external hub surface are transferred to the hub lumen by the patient's, nurse's, or physician's fingers when the catheter hub is handled (De Cicco et al., Lancet 2:1258-1260 (1989)). Even 10-20% of piggyback side-ports punctured six times daily become colonized with pathogenic microorganisms (Brismar et al., Clin. Nutr. 6:31-36 (1982).
Current hub designs were designed primarily to ensure a tight connection with intravenous tubing, but were not designed specifically to prevent hub and endoluminal catheter microbial colonization. Prevention of hub colonization, and therefore of hub-mediated infections is dependent on the avoidance of contamination during connection/disconnection of tubing, during direct injections, and during blood drawing as well as protection against contamination of the hub while connected to tubing. Experimental evidence has shown that intentional hub surface bacterial contamination leads to 100% internal fluid pathway contamination in an inappropriately disinfected hub and that disinfection of the hub cap will prevent up to 99% of potential contamination of the internal fluid pathway (Ardulno et al., Am. J. Infect. Control 26:377-380 (1997)). Needleless systems now in current use may also result in increased infection risk when compared to previous needled systems (Danzig et al., JAMA 273:1862-1864 (1995); Kellerman et al., J. Pediatr. 129:711-717 (1996)). These systems differ from older needle-containing systems by nature of their hub design.
Therefore, prevention of hub colonization will reduce or prevent the introduction of microorganisms into the catheter lumen. Such prevention may be evoked through careful cleaning and preparation of the catheter prior to use. Often however, such care is less than optimal and, in an emergency situation especially, catheter hubs are not often cleaned appropriately (Stotter et al., JPEN 11: 159-162 (1987); Sitges-Serra, Support Care Cancer 7:391-395 (1999)). Neither the currently used Luer-lock connector or the rubber membrane “piggyback” system have antimicrobial properties and therefore require strict aseptic manipulation. In addition, proper hub care requires additional training and increases the time required for already constrained health care professionals.
Thus, there exists a need for techniques and devices that can be effective at reducing microbial contamination of a catheter connection. The present invention satisfies this need and provides related advantages as well.